Arginine derivatives

H. Schmidt, T.D. Warner, K. Ishii, H. Sheng, and F. Murad, Insulin-secretion from pancreatic B-cells caused by L-arginine derived nitrogen-oxides. Science 255, 721—723 (1992). 

R. Ramage, J. Green, A.J. Blake, An acid labile arginine derivative for peptide synthesis NG-2,2,5,7,8-pentamethylchroman-6-sulphonyl-L-arginine, Tetrahedron 47(1991)6353-6370. 

Protein amino acids L-alanine L-arginine Arginine-derived alkaloids True alkaloids... 

Arecoline 40, 71, 86, 208, 209 Arginine-derived alkaloids 62 Aromatic alkaloids 10 Arosine 22 Arthropod alkaloids 6 Arundacine 8, 38 Arundamine 8, 38 Aspidoalbine 16, 38 Aspidolimidin 16, 68 Aspidolimidine 16... 

Chemical Class L-Arginine derivative thrombin inhibitor Clinical Pharmacology ... 

Pellat, C., Henry, Y., and Drapier, j. C. (1990). IFN-gamma-activated macrophages Detection by electron paramagnetic resonance of complexes between L-arginine-derived nitric oxide and nonheme iron proteins. Biochem. Biophys. Res. Commun. 166, 119-125. 

JV-Acetyl-n-phenylalanine derivatives, 25° (23). l JV-Benzoyl-u-arginine derivatives, 25° (24). 

Fluoromethyl ketones are one of the most widely used classes of peptidyl a-fluoroalkyl ketones, second only to trifluoromethyl ketones. Peptidyl fluoromethyl ketones are very effective as irreversible inhibitors of cysteine proteases the first reported use of a fluoromethyl ketone compound was the use of Z-Phe-Ala-CH2F as an irreversible inhibitor of cathepsin BJ2,31 Today, many lysine and arginine derivatives have been synthesized as potential inhibitors for trypsin and trypsin-like enzymesJ3 There are four basic methods for the synthesis of peptide fluoromethyl ketones (1) the reaction of HF with peptide diazomethyl ketones (Section 15.1.4.1.1), (2) a halogen-exchange reaction with a chloro-, bromo-, or iodomethyl ketone (Section 15.1.4.1.2), (3) a Henry nitro-aldol condensation reaction (Section 15.1.4.1.3), and (4) a modified Dakin-West acylation reaction (Section 15.1.4.1.4). 

Argatroban is a synthetic arginine derivative that is a competitive inhibitor of the action of thrombin on fibrinogen. It is given parenterally and monitored by the APTT test. It has a short half-life, It is nonantigenic, It is approved for use in HIT and has undergone trials for PCI in some patients Gable I) (24). 

Except for the arginine derivative, solutions of preactivated amino acids can be prepared and used for an entire week. Dissolve most of the amino acid derivatives in amine-free NMP at a concentration of 0.3 M. Due to poor solubility, derivatives of serine, threonine, tryptophan, and proline must be dissolved in amine-free DMF. The solutions can be stored at —20°C for at least 1 wk. Use... 

Prepare a 0.9 M solution of HOBt in amine-free NMP. Dissolve the Fmoc-amino acids or desired protected building blocks with the HOBt-solution to a concentration of 0.45 M. Except for the arginine derivatives, these solutions can be stored at -20°C for at least a week. Each day, prepare a 20% mixture of DIC in amine-free NMP. Use the fresh amino acid/HOBt solution every day and discard the previous one. To these solutions add 20% DIC/NMP at a ratio of 3 1 (e.g., 75 pL amino acid solution and 25 p,L DIC mixture prepared fresh every day) (see Note 3). 

It is well known that synthetic arginine esters, such as NQ -tosyl-L-arginine methyl ester (TAME), are hydrolyzed by thrombin and inhibit the clotting activity of thrombin. Since the binding specificities of arginine derivatives would be determined by the structure of both sides of arginine, i.e., amino as well as carboxyhc sides, a series of studies were undertaken by Okamoto et al. [104-106] to obtain potent and specific inhibitors of thrombin by modifications of the Na-substituent and methyl ester positions of TAME. 

Carboxyl-Containing Amide Derivatives of Ncc-Substituted L-Arginine Derivatives... 

For another group of Na-substituted L-arginine derivatives (47), Eq. 9 was formulated using the molar refractivity of the whole molecule [ 112], the CMR was found to have high correlation with C log P r = 0.837). Hence, another equation was derived (Eq. 40), where... 

Scheme 2 8-Lactam Formation with Carboxyl-Activated Arginine Derivatives when R = = R3 = H, or...

Besides the use of Z-Arg(HX)-OH (X = Q, Br),fi5] Boc-Arg(HCl)-OH,ti and Z-Arg(HC104)-0HP l for incorporation of the arginine residue, Z-Arg(N02)-OH (see Section 2.6.1.2) and Z-Arg(Z)2-OH (see Section 2.6.1.3.3) are useful for this purpose. After N -deprotection or, in the case of the two latter arginine derivatives, N -deprotection, subsequent chain-elongation steps are performed with the protonated arginine residues, as shown in Scheme 4 for the synthesis of a subfragment of somatostatin-28.t l This protonated arginine approach is well-suited for peptide synthesis in solution and has been successfully... 

Depending upon whether mono-A -, bis-A -, or bis-A -arginine derivatives are used, the efficiency of urethane protecting groups in terms of side reactions (see Section 2.6.1.2) varies to a great extent. Moreover, the orthogonality of this type of protection over N -protection is... 

Scheme 6 Cyclization of A -Bis(Adoc)arginine Derivatives to 4-Carboxy-2-imino-l,3-diazacycloheptane Compoundsl 1...

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